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Nicardipine

Class: Dihydropyridines
- Calcium-Channel Blocking Agents, Dihydropyridine
- Dihydropyridine Calcium-Channel Blocking Agents
- Calcium Antagonists
VA Class: CV200
CAS Number: 54527-84-3
Brands: Cardene

Medically reviewed by Drugs.com. Last updated on Apr 8, 2019.

Introduction

Calcium-channel blocking agent; dihydropyridine derivative.1

Uses for Nicardipine

Hypertension

Oral management of hypertension (alone or in combination with other classes of antihypertensive agents).1 2 3 1200

Therapy with extended-release capsules generally is preferred because of less frequent dosing, potentially smoother BP control,500 1200 and concerns raised by experience with short-acting (conventional, immediate-release) nifedipine.35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 61 72 73

Calcium-channel blockers are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include ACE inhibitors, angiotensin II receptor antagonists, and thiazide diuretics.501 502 503 504 1200 While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501 502 503 504 1200 1213

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).501 502 503 504 515 1200 1201

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.1200 (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.1200 However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.501 503 504 505 506 507 508 515 523 526 530 1200 1201 1207 1209 1222 1223 1229

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, an SBP goal of <130 mm Hg is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.1200 These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.1200 1202 1210

Other hypertension guidelines generally based target BP goals on age and comorbidities.501 504 536 Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients501 504 536 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.1222 1223 1224 1229

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.1200 1220 1229

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 1207 ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.1200

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).1200

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.1200

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.1200 Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.502 1200

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.1200 Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.1200

Calcium-channel blockers may be beneficial in hypertensive patients with certain coexisting conditions (e.g., ischemic heart disease)523 and in geriatric patients, including those with isolated systolic hypertension.502 510 1200

Calcium-channel blockers may be particularly useful in black patients with hypertension;100 101 501 504 1250 1251 1252 1253 1254 1255 such patients generally respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to other antihypertensive drug classes (e.g., ACE inhibitors, angiotensin II receptor antagonists).501 504 1200 However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.1200

IV, short-term management of hypertension when oral therapy is not feasible or desirable.18

IV management of hypertensive crises (e.g., emergencies) in adults.18 1200

IV, rapid reduction of BP in the management of acute severe hypertension and life-threatening symptoms in children and adolescents.1150

Angina

Management of chronic stable angina pectoris (alone or in combination with other antianginal agents).1 3 25

Nicardipine Dosage and Administration

General

BP Monitoring and Treatment Goals

  • Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.1200

  • If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.1200 1216

  • If adequate BP response not achieved with a single antihypertensive agent, either increase dosage of single drug or add a second drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., ACE inhibitor, angiotensin II receptor antagonist, thiazide diuretic).1200 1216 Many patients will require ≥2 drugs from different pharmacologic classes to achieve BP goal; if goal BP still not achieved with 2 antihypertensive agents, add a third drug.1200 1216 1220

Severe Hypertension and Hypertensive Emergency

  • Adults with a compelling indication—severe preeclampsia or eclampsia or pheochromocytoma crisis: Reduce SBP to <140 mm Hg during the first hour.1200

  • Adults with a compelling indication—acute aortic dissection: Reduce SBP to <120 mm Hg within the first 20 minutes.1200

  • Initial goal of IV therapy in adults with a hypertensive emergency without a compelling indication is to reduce SBP by ≤25% within the first hour, followed by further BP reduction if stable to 160/110 or 160/100 mm Hg within the next 2–6 hours, avoiding excessive declines in BP that could precipitate renal, cerebral, or coronary ischemia.1200 If this BP is well tolerated and the patient is clinically stable, may implement further gradual reductions toward normal BP in the next 24–48 hours.1200

  • Children and adolescents: Reduce BP by ≤25% of the planned reduction over the first 8 hours.1150

Administration

Administer orally1 2 5 or by IV infusion.18 22 23

Oral Administration

Conventional Capsules

Administer orally 3 times daily.1

Extended-release Capsules

Administer orally twice daily.2

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by slow, continuous IV infusion.18 22 23

Some experts state drug may be administered by direct IV (“bolus”) injection in children and adolescents with acute severe hypertension and life-threatening symptoms.1150

Must dilute commercially available injection concentrate containing 2.5 mg/mL with a compatible IV infusion solution prior to administration.18

Alternatively, administer as premixed solution (0.1 mg/mL in either 4.8% dextrose or 0.86% sodium chloride injection, 0.2 mg/mL in either 5% dextrose or 0.83% sodium chloride injection).600 601

If administered via a peripheral vein, change infusion site every 12 hours to minimize risk of venous irritation.18

Monitor BP closely during and after completion of IV administration; avoid rapid or excessive reduction in systolic or diastolic BP.18

Dilution

Injection concentrate: Dilute each 25-mg ampul containing 2.5 mg/mL with 240 mL of a compatible IV solution (see Solution Compatibility under Stability) to provide a solution containing 0.1 mg/mL.18 c

Dosage

Available as nicardipine hydrochloride; dosage is expressed in terms of the salt.a b c

Pediatric Patients

Acute Severe Hypertension†
Rapid Reduction of BP†
IV

Direct IV (“bolus”) injection: 30 mcg/kg (up to 2 mg) per dose.1150

IV infusion: 0.5–4 mcg/kg per minute.1150

Adults

Hypertension
Conventional Capsules
Oral

Initially, 20 mg 3 times daily.1 5

Adjust dosage according to patient’s peak (approximately 1–2 hours after dosing, particularly during initiation of therapy) and trough (8 hours after dosing) BP responses, but generally no more frequently than at 3-day intervals.1

Usual dosage is 20–40 mg 3 times daily.1

Extended-Release Capsules
Oral

Initially, 30 mg twice daily.2

Adjust dosage according to BP response 2–4 hours after dosing as well as just prior to next dose.2

Usual dosage range is 30–60 mg twice daily.2 1200

Switching to Extended-Release Capsules
Oral

Total daily dose of conventional tablets not a useful guide to judging effective dose of extended-release capsules.2 c However, may administer the currently effective total daily dose of conventional capsules and adjust dosage according to BP response.2 c

Short-term Management with IV Therapy
IV

Initially, 5 mg/hour.18

If target BP is not achieved, increase rate by 2.5 mg/hour every 15 minutes, up to 15 mg/hour.18

For more rapid reduction, initially, 5 mg/hour. If the target BP is not achieved, increase rate by 2.5 mg/hour every 5 minutes, up to 15 mg/hour.18

Following achievement of desired BP response, decrease rate to 3 mg/hour;18 adjust rate as necessary to maintain desired BP response.18

Conversion From Oral to IV Therapy
IV
Recommended Infusion Rates for Patients Previously Maintained on Oral Therapy.

Oral Dosage (as Conventional Capsules)

Equivalent IV Infusion Rates

20 mg every 8 hours

0.5 mg/hour

30 mg every 8 hours

1.2 mg/hour

40 mg every 8 hours

2.2 mg/hour

Hypertensive Emergency
IV

5–15 mg/hour; adjust according to BP response and tolerance.1200

Angina
Conventional Capsules
Oral

Initially, 20 mg 3 times daily.1 5 Adjust dosage according to patient tolerance and response at ≥3-day intervals.1

Usual dosage range is 20–40 mg 3 times daily.1

Prescribing Limits

Adults

Hypertension
IV

15 mg/hour.18

Special Populations

Hepatic Impairment

Conventional capsules: Initially, 20 mg twice daily in patients with severe hepatic impairment.1 Individualize dosage, but maintain a twice-daily dosing schedule.1

IV infusion: Consider dosage reduction.18 Use with caution in patients with portal hypertension.18

Renal Impairment

Conventional capsules: Initially, 20 mg 3 times daily.1 5 Titrate dosage carefully.1

Extended-release capsules: Initially, 30 mg twice daily.2 Titrate dosage carefully.2

IV infusion: Titrate dosage carefully.18

Geriatric Patients

Cautious dosing recommended.a b For conventional and extended-release capsules, initiate therapy at low end of dosage range.20 68

Cautions for Nicardipine

Contraindications

  • Known hypersensitivity to nicardipine or any ingredient in the formulation.1 2 18

  • Advanced aortic stenosis, since reduction in diastolic pressure may worsen myocardial oxygen balance.1 2 18

Warnings/Precautions

Warnings

Increased Angina

Increased frequency, duration, and severity of angina upon initiation or dosage increase of calcium channel blockers.1 2 18

Heart Failure

Use with caution in patients with heart failure or substantial left ventricular dysfunction, especially in those receiving concomitant β-adrenergic blocking agents.1 2 18

β-Blocker Withdrawal

Taper dosage of β-adrenergic blocking agent, preferably over 8–10 days before initiation of nicardipine.1 2 18 Nicardipine is not a β-adrenergic blocking agent and offers no protection against abrupt withdrawal of these agents.1 2 18

General Precautions

Hypotension

Possible symptomatic hypotension from decreased peripheral resistance.1 2 18 Use with caution in patients with acute cerebral infarction or hemorrhage; avoid systemic hypotension in these patients.1 2 18

Monitor BP carefully, especially during initiation of therapy or upward adjustment of dosage.1

Pheochromocytoma

Limited clinical experience in patients with hypertension associated with pheochromocytoma.18 Use with caution.18

Specific Populations

Pregnancy

Category C.1 2 18

Lactation

Distributed into milk in high concentrations in rats.1 2 18 Use not recommended.1 2 18

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 2 18

Some experts recommend use in children and adolescents for acute severe hypertension with life-threatening symptoms.1150

Use with caution for rapid reduction of BP in children and adolescents; may cause reflex tachycardia.1150

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.a b Select dosage with caution; initiate dosage at lower end of recommended range.a b

Hepatic Impairment

Use with caution in patients with hepatic impairment or reduced hepatic blood flow; dosage adjustments recommended.1 2 18 24 (See Hepatic Impairment under Dosage and Administration.)

Use of extended-release capsules has not been studied in patients with severe hepatic impairment.2

Renal Impairment

Use with caution; careful dosage titration recommended.1 2 18 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

With oral therapy, pedal edema, dizziness, headache, asthenia, flushing, increased angina, vasodilation, palpitation.a b

With IV therapy, headache, hypotension, nausea/vomiting, tachycardia.c

Interactions for Nicardipine

Specific Drugs

Drug

Interaction

Comments

Antacids (magnesium hydroxide)

Pharmacokinetic interaction unlikely1 2 18

β-Adrenergic blockers (e.g., propranolol)

Pharmacokinetic interaction (e.g., effect on plasma protein binding of nicardipine) unlikely1 2 18

Cimetidine

Increased plasma nicardipine concentrations1 2 18

Monitor carefully1 2 18

Cyclosporine

Increased plasma cyclosporine concentrations1 2 18

Monitor plasma cyclosporine concentrations closely and adjust dosage accordingly1 2 18

Digoxin

Potential for increased plasma digoxin concentrations1 2 18

Monitor serum digoxin concentrations1 2 18

Dipyridamole

No effect on plasma protein binding of nicardipine1 2 18

Fentanyl

Potential for severe hypotension with concomitant use of a β-adrenergic blocker and a calcium channel blocker1 2 18

Increase circulating fluid volume if hypotension occurs1 2 18

Furosemide

No effect on plasma protein binding of nicardipine1 2 18

Naproxen

No effect on plasma protein binding of nicardipine1 2 18

Quinidine

No effect on plasma protein binding of nicardipine1 2 18

Warfarin

No effect on plasma protein binding of nicardipine1 2 18

Nicardipine Pharmacokinetics

Absorption

Bioavailability

Completely absorbed from the GI tract following oral administration; peak plasma concentrations of conventional and extended-release capsules are attained within 0.5–2 and 1–4 hours, respectively.1 2

Minimum plasma levels of equivalent doses of conventional and extended-release capsules are similar.2

Bioavailability of conventional capsules is about 35%;1 2 extended-release capsules have a slightly lower bioavailability, except at the highest doses.2

Food

High-fat meal decreases bioavailability of conventional and extended-release capsules.1 2

Special Populations

In patients with severe hepatic impairment, peak plasma concentrations and AUC increased by 1.8 and 4-fold, respectively, and terminal half-life prolonged to 19 hours.1 2

In patients with moderate renal impairment, peak plasma concentrations and AUC increased by 2- to 3-fold following administration of conventional or extended-release capsules.1 2

Distribution

Extent

Distributed into milk in rats.1 2

Plasma Protein Binding

>95%.1 2 18

Elimination

Metabolism

Extensively metabolized in the liver.1 2 18

Elimination Route

Excreted in urine (49–60%) and feces (35–43%).1 2 18

Half-life

Multi-phasic; terminal elimination half-life is 8.6 and 14.4 hours following oral and IV administration, respectively.1 2 18

Stability

Storage

Oral

Conventional Capsules and Extended-release Capsules

Light resistant containers at 15–30°C.a b

Parenteral

Injection Concentrate

20–25°C; protect from light.c Avoid exposure to increased temperatures.c

Premixed Injection for Infusion

20–25°C; protect from light, freezing, and excessive heat.600 601

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in sodium chloride 0.45% or 0.9%

Dextrose 5% in water with potassium chloride 0.3%

Sodium chloride 0.9%

Incompatible

Sodium bicarbonate 5%

Variable

Dextrose 5% in Ringer’s injection, lactated

Dextrose 5% in water

Ringer’s injection, lactated

Sodium chloride 0.45%

Drug CompatibilityHID
Admixture Compatibility

Compatible

Potassium chloride

Y-Site CompatibilityHID

Compatible

Amikacin sulfate

Aminophylline

Aztreonam

Butorphanol tartrate

Calcium gluconate

Cefazolin sodium

Chloramphenicol sodium succinate

Clindamycin phosphate

Co-trimoxazole

Dextran 40 in dextrose 5%

Diltiazem HCl

Dobutamine HCl

Dopamine HCl

Enalaprilat

Epinephrine HCl

Erythromycin lactobionate

Esmolol HCl

Famotidine

Fenoldopam mesylate

Fentanyl citrate

Gentamicin sulfate

Hetastarch in sodium chloride 0.9%

Hydrocortisone sodium succinate

Hydromorphone HCl

Labetalol HCl

Lidocaine HCl

Linezolid

Lorazepam

Magnesium sulfate

Methylprednisolone sodium succinate

Metronidazole

Midazolam HCl

Milrinone lactate

Morphine sulfate

Nafcillin sodium

Nesiritide

Nitroglycerin

Norepinephrine bitartrate

Penicillin G potassium

Potassium chloride

Potassium phosphates

Ranitidine HCl

Sodium acetate

Sodium nitroprusside

Tobramycin sulfate

Vancomycin HCl

Vecuronium bromide

Incompatible

Ampicillin sodium

Ampicillin sodium-sulbactam sodium

Cefepime HCI

Furosemide

Micafungin sodium

Variable

Ceftazidime

Heparin sodium

Actions

  • Inhibits transmembrane influx of extracellular calcium ions across the membranes of myocardial cells and vascular smooth muscle cells, without changing serum calcium concentrations.a b c

  • Peripheral arterial vasodilator; acts directly on vascular smooth muscle causing reduction in peripheral vascular resistance (afterload) and BP.a b c

Advice to Patients

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 2 18

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 2 18

  • Importance of informing patients of other important precautionary information.1 2 18 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

niCARdipine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

20 mg*

Nicardipine Hydrochloride Capsules

30 mg*

Nicardipine Hydrochloride Capsules

Capsules, extended-release

30 mg

Cardene SR

Chiesi

60 mg

Cardene SR

Chiesi

Parenteral

For injection, concentrate, for IV infusion

2.5 mg/mL*

Cardene I.V.

Chiesi

Nicardipine Hydrochloride Injection

niCARdipine Hydrochloride in Dextrose

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion

0.1 mg/mL (20 mg) in 4.8% Dextrose

Cardene I.V.

Chiesi

0.2 mg/mL (40 mg) in 5% Dextrose

Cardene I.V.

Chiesi

niCARdipine Hydrochloride in Sodium Chloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion

0.1 mg/mL (20 mg) in 0.86% Sodium Chloride

Cardene I.V.

Chiesi

0.2 mg/mL (40 mg) in 0.83% Sodium Chloride

Cardene I.V.

Chiesi

AHFS DI Essentials™. © Copyright 2020, Selected Revisions April 8, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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